Click here to close Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly. We suggest using a current version of Chrome, FireFox, or Safari.
EMBO J 2001 Dec 17;2024:7052-9. doi: 10.1093/emboj/20.24.7052.
Show Gene links Show Anatomy links

Phosphorylation of Nedd4-2 by Sgk1 regulates epithelial Na(+) channel cell surface expression.

Debonneville C , Flores SY , Kamynina E , Plant PJ , Tauxe C , Thomas MA , Münster C , Chraïbi A , Pratt JH , Horisberger JD , Pearce D , Loffing J , Staub O .

The epithelial Na(+) channel (ENaC) plays an essential role in the regulation of whole body Na(+) balance and blood pressure. The cell surface expression of this channel, a complex of three subunits (alpha, beta and gamma ENaC), has been shown to be regulated by hormones such as aldosterone and vasopressin and by intracellular signaling, including ubiquitylation and/or phosphorylation. However, the molecular mechanisms involving phosphorylation in the regulation of ENaC are unclear. Here we show by expression studies in Xenopus laevis oocytes that the aldosterone-induced Sgk1 kinase interacts with the ubiquitin protein ligase Nedd4-2 in a PY motif-dependent manner and phosphorylates Nedd4-2 on Ser444 and, to a lesser extent, Ser338. Such phosphorylation reduces the interaction between Nedd4-2 and ENaC, leading to elevated ENaC cell surface expression. These data show that phosphorylation of an enzyme involved in the ubiquitylation cascade (Nedd4-2) controls cell surface density of ENaC and propose a paradigm for the control of ion channels. Moreover, they suggest a novel and complete signaling cascade for aldosterone-dependent regulation of ENaC.

PubMed ID: 11742982
PMC ID: PMC125341
Article link: EMBO J

Species referenced: Xenopus laevis
Genes referenced: avp nedd4 nedd4l sgk1

References [+] :
Abriel, Defective regulation of the epithelial Na+ channel by Nedd4 in Liddle's syndrome. 1999, Pubmed, Xenbase